USP49

Chr 6

ubiquitin specific peptidase 49

NCBI Gene: 25862ENSG00000164663UniProt: Q70CQ1

Enables histone binding activity and peptidase activity. Involved in mRNA splicing, via spliceosome; negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; and protein deubiquitination. Predicted to be located in nucleoplasm. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

86
ClinVar variants
8
Pathogenic / LP
0.94
pLI score· haploinsufficient
0
Active trials
Clinical Summary— USP49
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 73 VUS of 86 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.35LOEUF
pLI 0.938
Z-score 4.05
OE 0.15 (0.07–0.35)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.62Z-score
OE missense 0.64 (0.58–0.71)
271 obs / 422.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.15 (0.07–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.58–0.71)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 4 / 26.5Missense obs/exp: 271 / 422.6Syn Z: 0.37

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS73
Likely Benign4
Benign1
8
Pathogenic
73
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
0
71
2
0
73
Likely Benign
0
4
0
0
4
Benign
0
1
0
0
1
Total07610086

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

USP49 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
USP49 mediates tumor progression and poor prognosis through a YAP1-dependent feedback loop in gastric cancer.
Liu Z et al.·Oncogene
2022
IGF2BP3-dependent N6-methyladenosine modification of USP49 promotes carboplatin resistance in retinoblastoma by enhancing autophagy via regulating the stabilization of SIRT1.
Li L et al.·Kaohsiung J Med Sci
2024
USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication.
Pan T et al.·Elife
2019
USP49 promotes the malignancy of triple-negative breast cancer cells by regulating PKMYT1 ubiquitination and stability.
Chen J et al.·Biochem Biophys Res Commun
2026
CDK5R1, GSE1, HSPG2 and WDFY3 as indirect epigenetic-sensitive genes in atrial fibrillation.
Infante T et al.·Eur J Clin Invest
2024
Effects of common germline genetic variation in cell cycle control genes on breast cancer survival: results from a population-based cohort.
Azzato EM et al.·Breast Cancer Res
2008Cohort
ResiDUBs: A deubiquitinating enzyme-based prognostic model identifies UBXN1 driving sorafenib resistance in liver cancer.
Li M et al.·Int Immunopharmacol
2026Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools